IMMUNOMODULATION OF PERITONEAL-MACROPHAGES BY GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN HUMANS

Colony-stimulating factors are growth factors which induce differentia tion of the hematopoietic stem cells. Granulocyte-macrophage colony-st imulating factor (GM-CSF) stimulates proliferation and improves functi ons of neutrophils and monocyte/macrophages. A macrophage submesotheli al stratum has been suggested to constitute the first line of peritone al defense. We have tested whether intraperitoneally administered GM-C SF could increase the number and activation of peritoneal macrophages in peritoneal dialysis patients. Eight stable patients injected 17 mu g of GM-CSF in each of their four daily CAPD bags over three days. The clinical status, the peritoneal effluent and peripheral blood cell co unt, membrane receptor expression, phagocytosis activity and cytokine levels were monitored at days 0. 1, 3, 10 and 28. GM-CSF administratio n caused a large increase in peritoneal macrophage number (89-fold mea n increase after 72 hr), returning to baseline seven days after withdr awal. GM-CSF triggered an increase in the expression of CD11b/CD18 (CR 3) and its counterreceptor CD54, indicating the cellular progression i nto a more activated state. Both the number of phagocytic cells (55+/- 15% to 83+/-10%, P <0.05) and the phagocytic index(137+/-29 to 255+/-6 1, P <0.01) were also augmented. Peritoneal effluent cytokine-chemokin e levels demonstrated an increase in IL-6 and MCP-1 levels. while TNF- alpha, IL-1. IL-8, MIP-1 alpha and RANTES were nor significantly alter ed. GM-CSF administration did not affect the peritoneal transport of w ater or solutes. Minor side-effects were registered in two patients. I n conclusion, intraperitoneal GM-CSF causes a marked and transient rec ruitment of primed macrophages into the peritoneum without inducing in flammatory parameters. GM-CSF should improve the peritoneal defensive capacity through potentiation of the effector functions of resident an d newly-recruited macrophages.